35 slides from Brainstorm Cell Therapeutics's technical presentation, Jul 8, 2020
Slide 1: KOL Webinar: Phase 2 trial with NurOwn for Alzheimer's Disease
Brainstorm Cell Therapeutics July 8, 2020 KOL Webinar Phase 2 trial with NurOwn for Alzheimer’s Disease
Slide 2: Agenda – KOL Webinar to Discuss NurOwn for Alzheimer's
Agenda – KOL Webinar to Discuss NurOwn for Alzheimer’s 8:15-8:25 Chaim Lebovits, CEO Brainstorm Ralph Kern, M.D., MHSc, President & CMO Brainstorm o Introduction and overview 8:25-8:40 Pr. Dubois, Salpétrière University Hospital o High prevalence of the disease worldwide o Great progress in diagnost
Slide 3: Brainstorm's Pipeline
Brainstorm’s Pipeline Indication Preclinical IND Enabling Phase 1 Phase 2 Phase 3 Next Milestones NurOwn® MSC-NTF Technology Platform Q4’20E ALS Top-line data Q4’20E Progressive MS Top-line data IND: Q2’20E Alzheimer’s Disease Phase 2: 2H’20E Parkinson’s Disease Huntington’s Disease Autism Spectrum
Slide 4: ALS Phase 2 Clinical Trial: Functional Outcomes
ALS Phase 2 Clinical Trial: Functional Outcomes Single dose NurOwn® slowed the rate of disease progression by improving the ALSFRS-R LS mean change in slope vs. pre-treatment slope A Change from post-treatment to pre-treatment slope B Change from post-treatment to pre-treatment slope A Change A Chan
Slide 5: ALS Phase 2: CSF Delivery of NTFs Confirmed
ALS Phase 2: CSF Delivery of NTFs Confirmed CSF Profile 2 Weeks Post Treatment Demonstrates Delivery of NTFs VEGF HGF LIF 1000 VEGF VEGF VEGF VEGF VEGF 600 HGF HGF HGF HGF 18 LIF LIF LIF 1000 10001000 1000 1000 900 600 600 600600 600 ** 18 18 18 18 18 *** ****** *** 16 900900 900 900900 * 16 *** ***
Slide 6: ALS Phase 2: CSF MCP-1 Reduction
ALS Phase 2: CSF MCP-1 Reduction MCP-1 (an inflammatory mediator) is Significantly Reduced 2 Weeks Post-Treatment MCP-1 SDF-1 50,000 CHIT-1 50 MCP-1 250 SDF-1 ** CHIT-1 *** 45,000 50,000 4550 250 * 4045 *** 200 ** 40,000 45,000 35,000 40,000 * 3540 200 NurOwn® 3035 150 MCP-1 Reduction (40%) 30,000 3
Slide 7: NurOwn's MOA Demonstrated in ALS- Relevant to Alzheimer's Disease
NurOwn’s MOA Demonstrated in ALS- Relevant to Alzheimer’s Disease Underlying pathologies NurOwn® MSC-NTF MOA of ALS, MS, and AD Neuroprotection Neuronal Degeneration ↑CSF miR-132, ↓CSF Caspase-3 Astrocyte Dysfunction and Loss of Enhanced delivery of NTFs Neurotrophic Support (NTFs) ↑CSF VEGF, HGF, L
Slide 8: Introducing Today's KOLs
Introducing Today’s KOLs French National Coordinator of AD Trial Principal Investigator of AD Trial Bruno Dubois, M.D., Ph.D. Philip Scheltens, M.D., Ph.D. Professor of Neurology: Salpétrière University Hospital Professor of Cognitive Neurology: Amsterdam UMC President: Scientific Committee of Franc
Slide 9: Agenda
Agenda 8:15-8:25 Chaim Lebovits, Chairman & CEO Brainstorm Ralph Kern, M.D., MHSc, President & CMO Brainstorm o Introduction and overview 8:25-8:40 Pr. Dubois, Salpétrière University Hospital o High prevalence of the disease worldwide o Great progress in diagnostic procedures o Disappointment with c
Slide 10: Alzheimer's Landscape
Alzheimer’s Landscape 1) High prevalence of the disease worldwide 2) Great Progress in diagnostic procedures 3) Disappointment with current treatment
Slide 11: A High Prevalence
A High Prevalence • >7.5M in EU • >5M patients in the US Every 65 seconds 35% of Americans age $7.9 trillion is the someone in U.S. ≥60 are most afraid of potential cost saving develops Alzheimer‘s developing AD or from early AD diagnosis disease dementia only for current (cancer 23%) population in
Slide 12: Significant Progress in Diagnostic Procedures
Significant Progress in Diagnostic Procedures The 2 types of biomarkers Pathophysiological markers = Diagnostic markers • Reflect in-vivo pathology (amyloid and tau changes) • Are present at all stages of the disease • Observable even in the asymptomatic state • Might not be correlated with clinical
Slide 13: AD Diagnosis Framework
AD Diagnosis Framework Clinical-biological entity Clinical Biological Clinical phenotype Biomarker positivity Typical AD: • CSF abeta • aMCI • CSF tau • Amnestic syndrome • CSF phosho tau of hippocampal type • amyloid PET • tau PET Atypical AD: • Posterior cortical • Logopenic variant • Frontal vari
Slide 14: Alzheimer's Disease: "Turning to the left"
Alzheimer’s Disease: “Turning to the left” Dubois B et al. Alz Dement 2016
Slide 15: Disappointment with Current Treatment Research
Disappointment with Current Treatment Research Last 20 years, more than 100 negative trials 1993-2001 Approvals 2006-2008 Failures 2011-2012 Failures 2015-2016 Failures • 1993: Tacrine (Cognex) first • GSK Serotonin 6 • Gamma secretases Semagacestat, • Roche MAO-Bi Sembragiline one approved, now off
Slide 16: Alzheimer's Disease: Current Phase 2 and Phase 3 trials
Alzheimer’s Disease: Current Phase 2 and Phase 3 trials Cummings et al. / Alzheimer’s & Dementia: Translational Research & Clinical Interventions 5 (2019) 272-293
Slide 17: Agenda
Agenda 8:15-8:25 Chaim Lebovits, Chairman & CEO Brainstorm Ralph Kern, M.D., MHSc, President & CMO Brainstorm o Introduction and overview 8:25-8:40 Pr. Dubois, Salpétrière University Hospital o High prevalence of the disease worldwide o Great progress in diagnostic procedures o Disappointment with c
Slide 18: The Use of Biomarkers to Advance NurOwn in Alzheimer's Clinical Trials
The Use of Biomarkers to Advance NurOwn® in Alzheimer’s Clinical Trials Prof. dr Philip Scheltens, FAAN, FEAN Amsterdam UMC Alzheimer Center Amsterdam
Slide 19: Contents
Contents o New emerging therapies o Biomarker progress o Brainstorm approach
Slide 20: Beyond amyloid-β targets and approaches
Beyond amyloid-β targets and approaches Alzheimer Center Amsterdam
Slide 21: Yearly increase in Alzheimer's clinical trials and agents 2016-2019
Yearly increase in number of Alzheimer’s disease clinical trials and agents between 2016-2019 +12% 156 139 Agents 135 132 Trials 115 112 105 93 2016 2017 2018 2019 Cummings et al., Alzheimer’s & Dementia: TRCI (2016, 2017, 2018, 2019)
Slide 22: Issues in drug development
W Issues in drug development REVIEW Open Access The “rights” of precision drug development 2 for Alzheimer’s disease a Jeffrey Cummings”, Howard H. Feldman’ and Philip Scheltens* Fig. 1. The rights of AD drug developenent
Slide 23: The right patients
The right patients ATN profiles Biomarker category A-T-N- Normal AD biomarkers A+T-N- Alzheimers pathophysiology A+T-N+ Alzheimers Alzheimer’s pathophysiology pathophysiological continuum* A+T+N- Alzheimers disease A+T+N+ Alzheimers disease A-T+N- Non- AD pathophysiology A-T-N+ Non- AD pathophysiolo
Slide 24: CSF amyloid and tau are linked to cognitive decline in AD
CSF amyloid and tau are linked to cognitive decline in AD Hansson Scientific Reports 2019
Slide 25: CSF Amyloid/Tau are linked to neuroinflammation and neurodegeneration
CSF Amyloid/Tau are linked to neuroinflammation and neurodegeneration Amyloid+/Tau+ linked to Amyloid+/Tau+ linked to neuroinflammation neurodegeneration (NfL and Neurogranin) MCP-1 NfL Neurogranin Nordengen et al. Journal of Neuroinflammation (2019) Mila-Aloma Alzheimer’s & Dementia (2020)
Slide 26: Neuroinflammation plays a key role in AD
Neuroinflammation plays a key role in AD…. Ising and Heneka Cell Death and Disease (2018) 9:120 Nature | Vol577 | 16January2020 | 399
Slide 27: …which is mediated by microRNA-132
…which is mediated by microRNA-132
Slide 28: NurOwn delivery of miR-132 addresses AD Pathology
NurOwn® delivery of miR-132 addresses AD Pathology NurOwn® MSC-NTF cells express and deliver miR-132, which is downregulated in AD miR-132-3p Expression Log2 Fold Change Normalized Relative FC = +4.06 of mir-132-3p miR-132 is miR-132 is Quantiles downregulated in upregulated in AD1 MSC-NTF cells3 NC
Slide 29: In conclusion
In conclusion NurOwn® • Has shown promising results in ALS by increasing NTFs and micro-RNA 132 • Which is downregulated in AD and is considered the right target in AD • Which mediates a large array of pathologies in AD • The upcoming trial includes the right patients, uses the right biomarker and i
Slide 30: Agenda
Agenda 8:15-8:25 Chaim Lebovits, Chairman & CEO Brainstorm Ralph Kern, M.D., MHSc, President & CMO Brainstorm o Introduction and overview 8:25-8:40 Pr. Dubois, Salpétrière University Hospital o High prevalence of the disease worldwide o Great progress in diagnostic procedures o Disappointment with c
Slide 31: BCT-201-EU Study Overview Prodromal to Mild Alzheimer's Disease Study
BCT-201-EU Study Overview Prodromal to Mild Alzheimer’s Disease Study Stacy Lindborg, Ph.D.
Slide 32: BCT-201-EU, AD Phase 2a Study
BCT-201-EU, AD Phase 2a Study Patient Selection: 40 participants with Prodromal to Mild AD at Medical Centers in France and the Netherlands • Clinical diagnosis of prodromal to mild dementia* at least 6 months prior to enrollment • MMSE 20-30, CDR global score 0.5-1.0 • CSF profile consistent with A
Slide 33: BCT-201-EU, AD Phase 2a Trial Design
BCT-201-EU, AD Phase 2a Trial Design 52 Week clinical trial 16-week treatment period, 26-week follow-up period, Primary Objective 8 weeks between treatments 12 & 14 weeks apart To evaluate safety and tolerability of 3 Intrathecal Collect CSF, In person administrations of Bone Marrow Collect CSF, Col
Slide 34: BCT-201-EU, Phase 2a Study Measurements
BCT-201-EU, Phase 2a Study Measurements Biomarkers: paired serum and CSF samples Interested in biomarker levels over time to explore: • Neurotropic, neurodegenerative and inflammatory factors (e.g., VEGF, HGF, NfL, NfH, MCP-1, IL-6) • Markers associated with amyloid deposition (e.g., ab40, ab42) • M
Slide 35: Question & Answer
Question & Answer Q A Question & Answer 37 35